Wave phenomena in neuronal tissue may be fundamental to the normal functioning brain. Recently, a pattern of dynamic interaction between excitatory and inhibitory neurons ('transient imbalance episodes', or TIEs) has been identified by the PIs. We propose to study whether TIEs underlie wave phenomena in neuronal tissue. Experimentally, state-of-the-art voltage-sensitive dye imaging techniques will be combined with multiple whole-cell electrophysiological measurements to observe propagating neuronal activity at both a macroscopic and microscopic scale simultaneously. In addition, externally-applied electric fields will be used to perturb and interact with wave activity in order to test hypotheses regarding the underlying fundamental mechanisms. In computational and theoretical efforts, TIEs will be modeled based on novel mechanisms, most notably a dynamic extracellular potassium concentration and depolarization block. A separate model, designed to study the effects of externally-applied electric fields on neuronal interactions, will be developed. Ultimately, these models will be merged in order to investigate and make testable predictions about propagation phenomena and excitatory-inhibitory interplay in accordance with the experimental plan. Specific hypotheses are: (1) TIEs between excitatory and inhibitory layers are triggered by fluctuations in extracellular potassium concentration; (2) TIEs between excitatory and inhibitory layers propagate spatially; and (3) modulation of TIEs alters propagation phenomena. Intellectual merit: The PIs form an interdisciplinary team that brings together expertise in physics, mathematics, neuroscience and electrophysiology. Our long-term goal is to understand the spatiotemporal structure of neuronal activity, including cortical oscillations associated with perception, and as such, our results will provide a foundation for understanding the fundamental mechanisms of cognitive processing. Accordingly, our results will be of interest to the physics, mathematics, and neuroscience communities. Broader impact: The PIs will continue to involve students at all levels, including high school, graduate, and postdoctoral students. Results, including computational models, will be disseminated broadly via web pages, journal publications, and a range of scientific conferences spanning the physics, mathematics, and neuroscience communities. It may also be noted that the P1 is from an underrepresented group (Hispanic). [unreadable] [unreadable] [unreadable]